1. Field of the Invention
The invention relates generally to methods for treating acute pancreatitis in patients. The methods comprise administering a therapeutically effective amount of a pharmaceutical composition comprising secretin and a pharmaceutically acceptable carrier.
2. Brief Description of the Related Art
Acute pancreatitis is an inflammation of the pancreas that occurs when digestive enzymes leak out of the pancreatic ducts and damage the pancreas. The etiology of acute pancreatitis is unknown. It is a syndrome, which may result from multiple factors. The common feature to all cases of acute pancreatitis is a release and activation of digestive enzymes within the exocrine pancreas gland causing inflammation, injury, autolysis and necrosis to the organ. This can also lead to hemorrhage and pseudocyst formation within the gland. Severe upper abdominal pain, nausea and vomiting are the most common symptoms.
Approximately one-third of acute pancreatitis cases are associated with alcohol abuse, one-third with pancreatic cancer and one-third lack concomitant medical conditions and are considered idiopathic. Episodes of acute pancreatitis tend to recur with resulting hospitalizations and morbidity. Many patients develop chronic pancreatitis with ongoing low-grade inflammation of the pancreas, progressive destruction of glandular tissue, anatomical deformities, loss of organ function and digestive capabilities, and chronic pain.
Treatment of acute pancreatitis is medical not surgical and supportive in nature including intravenous fluids, analgesia and sometimes antibiotics.
Secretin is contraindicated in its FDA labeling for use during episodes of acute pancreatitis. This proscription is based on the belief that secretin stimulation of the exocrine pancreas with increased production of water and bicarbonate and greater flow of pancreatic juice containing proteolytic, digestive enzymes through the pancreatic ducts would exacerbate acute pancreatitis and predispose to the formulation of cysts, pseudocysts, and parenchymal necrosis.
Published studies in animal models of the use of secretin with acute pancreatitis are largely negative. Some preliminary studies of experimentally induced acute pancreatitis in rat and mouse models in the early 1980s reported a possible beneficial effect (Renner I G et al., J. Clin. Invest. 72(3):1081-92, 1983; Niederau C et al., Gasteroenterology 88(5, Pt1):1192-1204 1985; Renner I G et al., Dig. Dis.Sci. 31(3):305-313, 1986). Later, more definitive studies with cerulein-induced and reflux-induced acute pancreatitis models were negative (Keim V et al., Hepatogastroenterology 32(2):91-96, 1985; Infatino A et al., Res. Exp. Med. 190(2):89-93, 1990), as was a study of secretin for sodium taurocholate-induced acute pancreatitis in rat (Lankisch P G et al., Digestion 26(4):187-191, 1983).
A clinical study from Spain published in 1989 suggested secretin might produce some pain relief in acute pancreatitis (Manso M A et al., Peptides 10(2):255-260, 1989). However, the results of this study were not definitive. The only randomized, double-blind, placebo-controlled trial of secretin for therapeutic use evaluated patients with chronic pancreatitis with acute exacerbations and used a depot formulation of secretin (Tymper F., et al., Hepatogastroenterology 33(4): 159-162, 1986).
Additional examples of treatments for acute pancreatitis in the patent literature include the following:
U.S. Pat. No. 4,443,434 assigned to American Home Products discloses a method for treatment of acute pancreatitis comprising administering an octapeptide in an amount sufficient to inhibit pancreatic enzyme secretion. The octapeptide reduces gastric acid secretion, gastric blood flow and pancreatic enzyme release.
U.S. Published Patent Application No. US2001/0018049 assigned to Allergan Inc., discloses a method of treating a patient suffering from acute pancreatitis by administering an effective amount of a chimeric protein containing an amino acid sequence-specific endopeptidase activity. The chimeric protein ultimately inhibits zymogen release from acinar cells. This results in the reduction or elimination of the autodigestion of pancreatic tissue.
U.S. Pat. No. 6,143,306 assigned to Allergan Sales, Inc., discloses a non-radio therapy therapeutic method of treating disorders of the pancreas such as pancreatitis using a neurotoxin such as botulinum toxin.
U.S. Pat. No. 6,261,572 assigned to Allergan Sales, Inc., discloses a method for treating a pancreatic disorder by local administration of a therapeutic amount of a neurotoxin such as botulinum toxin, into or onto the body of the pancreas in order to treat symptoms of a pancreatic disorder.
U.S. Pat. No. 5,094,837 assigned to Wayne State University discloses a method for using magnetic resonance imaging (MRI) to image the pancreas by using secretin. An amount of secretin is placed in solution and administered to a patient for the purpose of pancreatic imaging. Administration of the secretin is done by IV infusion. The secretin employed in this method can be extracted from porcine or bovine sources or can be genetically recombined porcine, bovine or human secretin.
U.S. Pat. No. 6,020,310 and U.S. Pat. No. 6,498,143, both assigned to Repligen, disclose use of secretin to stimulate pancreatico-biliary fluid secretion in a patient exhibiting autism.
U.S. Pat. No. 6,197,746 assigned to Repligen Corporation discloses methods of using secretin for treating autism.
U.S Pat. No. 6,365,593 assigned to Repligen Corporation discloses methods of diagnosing individuals for autistic disorders, comprising obtaining a sample of urine from the individuals; measuring a level of a methylxanthine in the urine sample; and comparing the level to a normal control or to a threshold level.
U.S. Pat. No. 6,534,063 to Joan Fallon discloses methods of utilizing the fecal chymotrypsin level of an individual as a measure of the success of secretin, other neuropeptides, and peptides or digestive enzyme administration to such individuals, and in particular, as a prognosticative of potential secretin, other neuropeptides, peptides, and digestive enzyme administration for persons having ADD, ADHD, Autism and other PDD related disorders.
None of the treatments currently utilized for acute pancreatitis, have proven to be very effective or have changed the course of the disease. However, the present invention is believed to be an answer to these needs.